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Page 1: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

because you depend upon results © Abacus ALS© Abacus ALS

Allergy Update

© Abacus ALS

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because you depend upon results © Abacus ALS© Abacus ALS

ImmunoCAP sIgG

measurement

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ImmunoCAP Specific IgG

Measures antigen-specific IgG antibodies in human

serum and plasma.

Part of the natural defence system of the body and

develop in response to contact with foreign substances.

Marker of exposure to that antigen.

Level of specific IgG in serum usually reflects the extent

of exposure to that antigen.

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Expected test values

No common cut-off value for specific IgG antibodies

Markers for antigen exposure and are not directly related to the disease.

Results vary both within and between antigens.

Geographical variations are also important, as are individual levels of exposure.

To determine if levels are increased, the reference level of specific IgG antibodies to a certain antigen should be measured in a number of samples from normal healthy persons and, if possible, compared with the levels in a group of patients.

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Valuable Clinical Information

Allergic disease

• In clinical studies with asthma, rhinitis, urticaria, eczema

and gastrointestinal disorders

• As a marker for exposure in different lung diseases, e.g.

allergic alveolitis, aspergilloma and aspergillosis

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Background: Exposure to organic dust produced by

birds often gives rise to an immune response, e.g. IgG

antibodies, but intense exposure can lead to high

concentrations of IgG antibodies and the development of

allergic alveolitis, often known as ‘bird fancier’s lung’.

Conclusion: Threshold values […] were 9.8, 10.8 and 10.0

mg/l for pigeons, budgerigars and parrots, respectively.

Page 7: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

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Page 8: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

because you depend upon results © Abacus ALS© Abacus ALS

Pulmonary Aspergilloma

Mass caused by a fungal infection that usually grows in

lung cavities.

Formed when the fungus Aspergillus grows in a clump in a

lung cavity, or invades healthy tissue, causing an abscess.

The most common species of fungus that causes disease

in humans is Aspergillus fumigatus.

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Symptoms & Exams

When symptoms do

develop, they can include:

• Chest pain

• Cough

• Coughing up blood

• Fatigue

• Fever

• Unintentional weight loss

Tests:

• Biopsy of lung tissue

• Blood test for presence of aspergillus in the body (galactomannan)

• Bronchoscopy or bronchoscopy with lavage

• Chest CT

• Chest x-ray

• Sputum culture

• Blood test to detect antibodies to aspergillus(serum precipitins for aspergillus) = sIgG Ab

Page 10: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

because you depend upon results © Abacus ALS© Abacus ALS

Allergic Bronchopulmonary aspergillosis

in cystic fibrosis patients

10% of patients with cystic fibrosis

For the diagnosis:

• Clinical deterioration

• Elevated Total IgE (>500IU/ml)

• Raised Ige to A. fumigatus

• Precipitins to A. fumigatus or sIgG to A. fumigatus OR

changes on chest X-ray not clearing with antibiotics and

physiotherapy

Page 11: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

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Prospective cohort study of 175 adult patients with chronic or allergic pulmonary aspergillosis.

Aspergillus IgG antibodies detected using CIE, PhadiaImmunoCap Aspergillus IgG and Bio-Rad PlateliaAspergillus IgG.

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Results:

• When compared with CIE, both ImmunoCap and Platelia Aspergillus IgG had good sensitivity (97 and 93%, respectively).

• The level of agreement between the two EIAs for positive results was good, but the concentration of antibodies was not correlated between the tests or with CIE

• titre.

• ImmunoCap IgG inter-assay coefficient of variation was 5%, whereas PlateliaIgG was 33%.

• Median ImmunoCap IgG values for CPA and allergic aspergillosis were 95 and 32 mg/L, respectively, whereas Platelia IgG values were >80 and 6 AU/mL.

• The direction of CIE titre change over 6 months was mirrored by ImmunoCapIgG levels in 92% of patients, and by Platelia IgG in 72% of patients.

Conclusion:

Both ImmunoCap and Platelia Aspergillus IgG EIAs are sensitive measures of Aspergillus IgG antibodies compared with CIE. However, ImmunoCap appears to

have better reproducibility and may be more suitable for monitoring patient disease.

Page 13: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

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Determination of Aspergillus specific IgG

antibodies using the Pharmacia UNICAP in airway diseases

MCPG Schinkel, MLV Watkins, PC Potter

Conclusion

1. The Pharmacia UNICAP assay discriminates between ABPA, CF, Asthmatics and normal individuals with elevated or normal total

IgE values.

2. The highest levels were found in ABPA. These levels were 115 ± 64.32mg/L (Aspergillus fumigatus) and 84.43 ± 48.27mg/L

(Aspergillus niger).

3. Higher levels were observed in both CF and ABPA than in the other groups.

4. Both Aspergillus fumigatus and Aspergillus niger should be tested in patients with CF and ABPA, as they appear to rise

concordantly.

5. The UNICAP IgG for Aspergillus is thus a convenient automated tool in ABPA and CF.

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Valuable Clinical Information

Immunotherapy

• Show a general (but not definitive) correlation with

clinical outcome

• Show that the immune system is responding to the

therapy

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Overview of the typical

allergic response

Page 16: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

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Specific immunotherapy

Page 17: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

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sIgG measurement in

Specific immunotherapy Effective immunotherapy specific induces IgG/IgG4 to

the allergens

Measurement of IgG/IgG4 during the course of SIT

treatment could add information about the individual

patient beneficial response to the treatment

If a patient should not respond with an induction of

competitive antibodies during immunotherapy a careful

re-evaluation of the treatment options could be useful.

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VENOM ALLERGY

Bee and/or wasp venom allergy and indications for VIT

Discover the connectionImmunoCAP® rApi m 10 honey bee venom component

Bee and/or

wasp venom

allergy

Indications

for VIT

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Matching VIT to the patient’s sensitization profile• Successful venom immunotherapy (VIT)

is more likely when treatment selection is based on specific sensitization to bee and/or wasp venom1

“As a paradigm, allergen immunotherapy is ‘specific’, meaning

that it only modifies the immune response against the allergen

for which the vaccination is being performed.”

WAO –ARIA – GA²LEN Consensus Paper on Molecular-based Allergy Diagnostics2

Bee and/or

wasp venom

allergy

Indications

for VIT

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Double positivity – Is it a genuine bee and/or wasp venom allergy?

*Cross-reactive Carbohydrate Determinants

Positive results with venom extracts do not always reflect

genuine sensitization3

In many cases IgE antibodies to CCDs* cause double

positivity, but rarely have clinical relevance1,3,4

Up to 50% of venom allergic patients have positive test results to both bee and wasp venom3

Page 21: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

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Double positivity – Is it a genuine bee and/or wasp venom allergy?

Genuine bee

venom allergy

Genuine wasp

venom allergy

rApi m1

rApi m10

Genuine double positivity

OR cross reactivity?

rVes v1

rVes v5

rPol d5?

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Discover the new ImmunoCAPhoney bee component rApi m 10Honey bee component Api m 10 can be absent or underrepresented in VIT extracts5 – VIT of patients sensitized to Api m 10 may be less efficient

Adding rApi m 10 to your test panel improves diagnostic specificity and precision, and supports more well-founded decisions for VIT6

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“Conclusion: Analysis of a panel of CCD-free HBV allergens improved diagnostic

sensitivity compared with use of rApi m 1 alone, identified additional major allergens,

and revealed sensitizations to allergens that have been reported to be absent or

underrepresented in therapeutic HBV preparations.”6

(n=144)

rApi m 1 + 10 improve diagnosis of genuine bee-venom sensitizationIncreases your possibility to resolve double positivity

72,2%

86,8%

60 70 80 90 100

Sensitivity (%)

rApi m 1

rApi m 1 + 10

Page 24: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

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ImmunCAP allergen componentshelp you resolve double positivityWith five CCD-free venom components you can

• Distinguish between true co-sensitization to bee and wasp, and CCD-dependent cross reactivity1,4,7,8

- Honey bee: rApi m 1 and rApi m 10- Common/paper wasp: rVes v 1, rVes v 5, rPol d 5

• Help match the VIT to the patient’s sensitization profile1,5,6

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WAO – ARIA – GA²LEN

recommends allergen component

testing“Detection of recombinant venom allergens can discriminate

between genuine venom sensitization and cross reactivity

due to CCDs in patients with double-positive IgE results from

traditional venom tests that are based on allergen extract”

WAO – ARIA – GA²LEN Consensus Paper on Molecular-based Allergy Diagnostics2

Page 26: Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes on chest X-ray not clearing with antibiotics and physiotherapy

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Identify suitable VIT – Suggested test algorithm

ImmunoCAP®

COMPLETE ALLERGENSHoney bee (i1) + Common Wasp (i3) + Paper Wasp (i77) ImmunoCAP Tryptase*

Honey bee Honey bee + Common/Paper wasp Common/Paper waspVIT CANDIDATE

ImmunoCAP

ALLERGEN COMPONENTSBee: rApi m 1 (i208), rApi m 10 (i217) Common/paper Wasp: rVes v 1(i211), rVes v 5 (i209), rPol d 5 (i210)

rApi m 1 and/or rApi m 10

positive

rApi m 1 and/or rApi m 10 + rVes v1 and/or rVes v5 and/or rPol d 5

positive positive

rVes v 1 and/or rVes v5 and/or rPol d5

positive

*Measure tryptase baseline levels before VIT to assess risk for severe reactions9

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A broad toolbox of ImmunoCAPallergen components

Over 100 allergen components that can help you:

Assess risk of systemic reactions in patients with food allergy2

Explain symptoms due to cross-reactivity2

Identify the appropriate immunotherapy for the individual patient2

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References: 1. Bonifazi F. et al & EAACI Interest Group on Insect Venom Hypersensitivity, Prevention and

treatment of hymenoptera venom allergy: guidelines for clinical practice. Allergy 2005; 60: 1459-1470. 2.

Canonica G.W. et al., A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics.

World Allergy Organ J. 2013; 6(1): 17. 3. Spillner E. et al., Hymenoptera allergens: from venom to ”venome”.

Frontiers in immunology 2014; 5: 1-7. 4. Biló B. et al & EAACI Interest Group on Insect Venom

Hypersensitivity., Diagnosis of Hymenoptera venom allergy. Allergy 2005; 60: 1339-1349. 5. Blank S. et al., Api

m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts.

Allergy 2011; 66: 1322-1329. 6. Köhler J et al. Component resolution reveals additional major allergens in

patients with honey bee venom allergy. J Allergy Clin Immunol 2014; 133: 1383-1389. 7. Müller U. et al.,

Hymenoptera venom allergy: analysis of double positivity to honey bee and Vespula venom by estimation of

IgE antibodies to species-specific major allergens Api m 1 and Ves v 5. Allergy 2009; 64: 543-548. 8.

Mittermann I. et al., Recombinant allergen-ased IgE testing to distinguish bee and wasp allergy. J Allergy Clin

Immunol 2010: 125: 1300-1307. 9. Rueff F et al. Predictors of severe systemic anaphylactic reactions in

patients with Hymenoptera venom allergy: Importance of baseline serum tryptase – a study of the EAACI

Interest Group on Insect Venom Hypersensitivity. J Allergy Clin Immunol 2009; 124: 1047-1054.